Filippi Syndrome

Synonyms of Filippi Syndrome

Syndactyly Type I with Microcephaly and Mental Retardation

General Discussion

Filippi syndrome is an extremely rare genetic disorder that may be apparent at birth (congenital). The disorder is characterized by an unusual facial appearance, abnormalities of the fingers and toes, and mild to severe mental retardation. Primary physical findings include growth delays, webbing or fusion (syndactyly) of certain fingers and toes, inward deviation or bending (clinodactyly) of the fifth fingers ("pinkies") and microcephaly, condition that indicates that the head circumference is smaller than would be expected for an infant's age and sex. Filippi syndrome is transmitted as an autosomal recessive trait.

Signs & Symptoms

Filippi syndrome is characterized by growth delays before and after birth (prenatal and postnatal growth retardation), a low birth weight, and short stature. Affected individuals also have characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance. Affected infants may often exhibit microcephaly, condition that indicates that the head circumference is smaller than would be expected for an infant’s age and sex

Individuals with Filippi syndrome also have malformations of the fingers and toes (digits). These may include webbing or fusion (syndactyly) of certain digits, such as the third and fourth fingers and/or the second, third, and fourth toes. Partial or complete webbing of these particular digits is sometimes referred to as “syndactyly type I.” The severity of the syndactyly may be variable, ranging from webbing of skin and other soft tissues to fusion of bone within the affected digits. Filippi syndrome may also be characterized by additional digital abnormalities. In some cases, there may be inward deviation (clinodactyly) of the fifth fingers (pinkies). In addition, the fingers and toes may appear unusually short (brachydactyly), particularly due to abnormalities of bones within the body of the hands and feet (metacarpals and metatarsals).

Individuals with Filippi syndrome have distinctive facial features including a high forehead, a broad bridge of the nose, thin nostrils, an abnormally thin upper lip and widely spaced eyes (hypertelorism).

Filippi syndrome is also characterized by mild to severe mental retardation and some affected individuals may have defective language and speech development, potentially resulting in an inability to speak.

Some individuals with the disorder may have additional physical abnormalities including delayed bone age, incomplete closure of the roof of the mouth (cleft palate) and a dislocated elbow. In some affected males, the testes may fail to descend into the scrotum (cryptorchidism). In one report, skin and teeth abnormalities were also noted.

Causes

Filippi syndrome is transmitted as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

Some cases of Filippi syndrome have had parents who were related by blood (consanguineous). All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Filippi syndrome is a rare genetic disorder that appears to affect males and females equally. Since the disorder was originally described in 1985 (G. Filippi), approximately 18 cases have been reported in the medical literature, including affected siblings within certain families (kindreds) as well as isolated cases.

Filippi syndrome is sometimes classified as one of the “craniodigital syndromes,” several disorders loosely grouped together because of similar abnormalities affecting the head and fingers and toes.

Related Disorders

Symptoms of the following disorders may be similar to those of Filippi syndrome. Comparisons may be useful for a differential diagnosis:

KBG syndrome is a rare genetic disorder characterized by mild to moderate mental retardation and speech defects, abnormalities of the head and facial (craniofacial) area, short stature, and additional skeletal malformations. Characteristic facial features include a relatively round face and short head (brachycephaly); broad eyebrows that grow together across the base of the nose (synophrys); a high nasal bridge; “bow-shaped” lips; and prominent ears. In addition, certain teeth may be abnormally large (macrodontia) whereas others may be absent (oligodontia). Skeletal abnormalities may include delayed bone age; abnormal shortness of certain bones of the fingers; webbing or fusion (syndactyly) of the second and third toes; or malformations of bones within the spinal column (vertebrae). KBG syndrome is inherited as an autosomal dominant trait. (For further information, choose “KBG” as your search term in the Rare Disease Database.)

Scott craniodigital syndrome is a rare genetic disorder characterized by mental retardation, distinctive abnormalities of the craniofacial area, and malformations of the fingers and toes (digits). Craniofacial features typically include a relatively short head (brachycephaly); a small, narrow nose; widely spaced eyes (ocular hypertelorism); and an abnormally small lower jaw (mandible). Affected infants and children may also have webbing or fusion of certain fingers and toes; abnormal skin ridge patterns (dermatoglyphic patterns) on the palms; and/or a foot deformity in which there is inward deviation of the heel (talipes varus). Additional characteristic features may include unusually thick scalp hair with an extended hairline; long, dark eyelashes; abnormally thick eyebrows; and generalized excessive hair growth (hirsutism). Scott craniodigital syndrome is thought to be inherited as an X-linked recessive trait. (For further information, choose “Scott craniodigital” as your search term in the Rare Disease Database.)

Blepharonasofacial syndrome is a rare genetic disorder characterized by distinctive facial abnormalities and mental retardation. Physical features typically include an abnormally increased horizontal distance between the inner angles (i.e., canthi) of the eyelids (telecanthus); downwardly slanting eyelid folds (palpebral fissures); an unusually “bulky” nose with a low nasal bridge; and a “trapezoidal” shaped upper lip with a pouting lower lip. In addition, facial expressions may seem fixed or mask-like. Affected individuals may also have poor coordination; abnormal looseness (laxity) of the joints; mild webbing or fusion (syndactyly) of soft tissues of the fingers; and a condition in which there is abnormal muscle stiffness (rigidity) with irregular, involuntary twisting or distorted posturing of affected muscles (torsion dystonia). Blepharonasofacial syndrome is inherited as an autosomal dominant trait.

There are additional congenital disorders that may be characterized by craniofacial abnormalities, webbing or fusion of certain fingers and toes, mental retardation, and/or other symptoms and findings similar to those potentially associated with Filippi syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)

Diagnosis

The diagnosis of Filippi syndrome may be made at birth or during early infancy based upon a thorough clinical evaluation and characteristic physical findings. Specialized testing, such as certain advanced imaging techniques, may also be conducted to detect or characterize particular findings that may be associated with the disorder.

Standard Therapies

Treatment

The treatment of Filippi syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals who may need to systematically and comprehensively plan an affected child's treatment. These professionals may include pediatricians; physicians who specialize in disorders of the skeleton, joints, muscles, and related tissues (orthopedists); and/or other health care professionals.

In some affected individuals, treatment may include surgical repair of certain skeletal or other abnormalities potentially associated with the disorder. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors.

Early intervention may be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education, physical therapy, speech therapy, or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for individuals with Filippi syndrome and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

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Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

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